# Regulation of Telomere Maintenance in Fission Yeast

> **NIH NIH R01** · UNIVERSITY OF ILLINOIS AT CHICAGO · 2023 · $34,580

## Abstract

Project Summary/Abstract
Our laboratory is interested in understanding how eukaryotic cells ensure the maintenance of
telomeres, the natural ends of linear eukaryotic chromosomes. Evolutionarily conserved shelterin and
CST (CTC1/Cdc13-STN1-TEN1) complexes play essential roles in telomerase recruitment and
protection of telomeres against DNA repair and checkpoint factors. Stable maintenance of telomeres is
critical to preserve genomic integrity and prevent the accumulation of undesired mutations that might
lead to tumor formation. Regulation of telomere structures and telomerase also affect cell proliferation
and tissue maintenance in aging organisms. Therefore, basic mechanistic studies investigating how
telomere and DNA damage response proteins collaborate in proper telomere maintenance should
provide critical insights necessary to help devise more effective treatment strategies against tumors or
other age-related diseases. Our proposed research projects utilize the fission yeast
Schizosaccharomyces pombe. Fission yeast telomeres serve as a good model for human telomeres
since proteins involved in telomere maintenance are highly conserved between fission yeast and
humans.
 Studies from our lab and others have provided detailed insights into how fission yeast shelterin and
Stn1-Ten1 ensure stable maintenance of telomeres in fission yeast. Those include findings that (1)
Tel1ATM/Rad3ATR-dependent phosphorylation of the shelterin subunit Ccq1 on Thr93 promotes
telomerase recruitment by promoting interaction between Ccq1 and the telomerase subunit Est1, and
(2) SUMOylation of another shelterin subunit Tpz1TPP1 on Lys242 facilitates Stn1-Ten1 recruitment to
telomeres and limits telomere extension. Evolutionarily conserved "TEL patch" residues within Tpz1
have also been found to promote telomerase activation and recruitment, further highlighting the well-
conserved nature of telomere regulation by fission yeast and mammalian shelterin. Our analyses of
temporal binding patterns for DNA polymerases, telomerase, shelterin, and Stn1 found that shelterin
subunits Rap1 and Poz1 and the Stn1-Ten1 complex promote timely dissociation of telomerase from
telomeres by promoting recruitment of Pola to complete lagging strand synthesis at telomeres. For the
current grant application, our proposed experiments will (1) identify and characterize the underlying
regulatory mechanism(s) that allow Ccq1 and Poz1 to promote Pola-dependent telomere protection
(Aim 1), (2) identify new interaction partners of Stn1-Ten1 complex and characterize their contributions
to recruitment/retention of Stn1-Ten1 complex at telomeres and non-telomeric sites (Aim 2), and (3)
investigate how regulation of TERRA vs. poly(A)+TERRA expression modulates Stn1-Ten1-Pola
recruitment at telomeres (Aim 3).

## Key facts

- **NIH application ID:** 10795564
- **Project number:** 3R01GM143316-01A1S1
- **Recipient organization:** UNIVERSITY OF ILLINOIS AT CHICAGO
- **Principal Investigator:** Toru Nakamura
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $34,580
- **Award type:** 3
- **Project period:** 2022-09-01 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10795564

## Citation

> US National Institutes of Health, RePORTER application 10795564, Regulation of Telomere Maintenance in Fission Yeast (3R01GM143316-01A1S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10795564. Licensed CC0.

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